Midterm 1 - Notes 5 (Part 1) Flashcards
If you have a SNP what does it tell you?
That you have increase likelihood that you will get a certain type of disease, not that you will actually get it
- they are not predictors
- the linkages are pretty weak so many things can contribute to getting the disease
What is low for many traits?
The contribution of individual allele to trait variation
What do GWAS do?
They only detect the genetics component of trait variation, not environmental
Comparative genomics
Rate of evolutionary change of each position across the genome
If we apply the comparative genomics method, what can we do?
Pinpoint sections that are genetically important
- higher chance of being functionally important (you would want to target these genes)
What do you need in for comparative genomics? (2)
- A lot of genome wide information (where polymorphism exists)
- Sequence information of many sequences from species
GERP
Genomic Evolutionary Rate Profiling
Genomic evolutionary rate profiling
Rates of change for each position across the genome
What does a high score of GERP mean?
Little change
- less important function because it is very conserved
What does a low score of GERP mean?
Lots of change
- functionally important
Where do most beta-thalassemia variants occur?
In small regions with high conservation
What does low rate of evolutionary change mean?
Functional important
What can low rate of evolutionary change be used to do?
Predict casual variants
What does GERP need? (2)
- Whole genome sequence information from many individuals
2. Closely related species
What are 2 types of functional data for prodicting impact of change?
- Promoter analysis
- eg. known/predicted cis elements - Protein sequence/structure analysis
What is promotor a model impact for?
Gene expression
What is protein sequence/structure analysis a model impact for?
Change for each codon
What does predicting impact on changes need? (4)
- Functional data on promoters
- Functional data on protein structures
- Whole genome sequence information from many individuals
- Closely related species
What do whole genome association/ linkage studies do? (4)
- Look for associated loci
- Classify polymorphisms into functional classes
- Predict impact on candidate SNPs
- Narrows down candidates
What are 2 problems with having too many associations?
- Missed/ weak associations
- contribution might be too small - Available markers to far way from casual differences for a given population
What are 2 possible solutions for having too many associations?
- Increase population size
2. Increase number of markers
What is an example of multiple genotyping approaches?
NGS
NGS
Next generation sequencing
Human genome project
Sequenced the complete human genome
What are 4 components you get from the whole genome sequencing?
- Association genetics
- Genome structure
- Comparative genomics
- Medical genomics
Association genetics (3)
- Polymorphism discovery
- basis for whole genome association studies - Allows jump from genetic to physical map
- candidate genes - Now polymorphism analysis
Genome structure (2)
- Frequency and distribution of genes, repetitive elements, viral integrations, etc…
- Whole genome duplications
Comparative genomics (2)
- Evolution of genes and gene families
- Loss and gain of genes on a global scale
- how did the new gens and functions evolve
Medical genomics (3)
- Predict/prevent disease
- Disease diagnosis
- Individualized treatment and medicine
- eg) pharmacogenomics
What is the genomic size of mRNA?
2,500bp
What is the genomic size of gene size?
20,000bp
What is the genomic size of E.coli?
5,000,000bp (5,000 genes)
